Cardiac conditions such as supraventricular arrhythmias (SVA) or chronic heart block are treated with device therapies, drug therapies, or a combination thereof. Device therapies typically involve implantable medical devices (IMDs). IMDs are effective except with some patients that experience SVA or chronic heart block. One such example relates to implantable pulse generators (IPGs) or implantable cardioverter-defibrillators (ICDs) that deliver electrical stimulation to the vagal nerve plexes located in the heart. Stimulation of vagal nerve plexes enhances parasympathetic input to the atrioventricular (AV) node and subsequently slows AV nodal conduction and ventricular rate. While this therapy operates acutely, tachyphylaxis may occur. Tachyphylaxis is a rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. Additionally, vagal stimulation may induce atrial arrhythmias.
Combined device and drug therapies are costly. One such therapy relates to ventricular rate sensors of an IMD that rely on a sensor-based algorithm to regulate the delivery of drugs. In this case, drugs are typically taken orally on a daily basis regardless of the existence of atrial fibrillation (AF) or inadequate ventricular rate in a heart. A daily dosage is problematic for some patients. For example, some patients are excessively bradycardiac while in sinus rhythm and experience an elevated ventricular rate in AF. To address this problem, a pacemaker is implanted to detect “drug induced brady” conditions and to control the rate of drug delivery. Pacemakers increase patients' costs.
Drug therapies also have drawbacks. Drugs are delivered through systemic circulation of a patient. Examples of systemic drug delivery include oral, intravenous, subcutaneous, or transdermal delivery methods. Since systemic drug delivery introduces drugs to all organs and tissue, non-targeted organs or tissue may exhibit drug toxicity. Drug toxicity concerns limit the dosage that is administered to a patient. Limiting a dosage may reduce the effectiveness of the drug. Systemic drug delivery may also cause side effects in the patient, which reduces tolerability or effectiveness of drugs. For example, drugs that slow down AV nodal conduction may cause side effects such as sinus bradycardia, congestive heart failure, fatigue, or constipation.
Some gene therapies claim to chronically transfect AV nodal tissue with specific genes to control conduction rate through the AV node. However, it is unclear whether these gene therapies adequately control titration of an agent to achieve therapeutic goals. Consequently, gene therapy may result in uncontrollable or inadequate AV nodal rate. It is therefore desirable to have therapies that overcome the limitations described above.